Melissenos (Greek: Μελισσηνός), latinized Melissenus, feminine form Melissene (Μελισσηνή), latinized Melissena, was the name of a noble Byzantine family that flourished from the late 8th century on until the end of the Byzantine Empire and beyond.
The Melissenoi are one of the oldest known aristocratic families of the middle Byzantine period. Genealogies from the 16th and 17th centuries trace the family to a patrikios Michael, relative of Michael I Rhangabe (reigned 811–813) and his son the magistros Leo, but the family stretches back another half-century to the general Michael Melissenos, a favourite of Emperor Constantine V (r. 741–775). This Michael married a sister of Constantine's wife, Eudokia, and their son, Theodore Kassiteras Melissenos, became Patriarch of Constantinople in 815–821.
The exact region of origin of the family is unknown, but in the 9th–11th centuries, they were mostly active in Asia Minor, serving as generals and governors of the local themes. In the late 11th century, the family seems to have had ties particularly with the area of Dorylaion in Phrygia, which may indicate that the family hailed from there.
The Melissenoi also appear to have maintained close ties to the other families comprising the military aristocracy (the dynatoi) of this period, which likewise mostly originated from Asia Minor. Thus, two of the Melissenoi, the doux of Antioch Leo and his brother Theognostos, supported the aristocratic revolt of Bardas Phokas the Younger in the early reign of Basil II (r. 976–1025). For the remainder of Basil's reign, the Melissenoi do not appear to have occupied high military posts, but they re-appear among the highest rungs of the aristocracy in the later 11th century, when a Theognostes Melissenos was katepano of Mesopotamia, while Maria Melissene was one of the few holders of the exalted title of zoste patrikia.